Method for measuring water exchange across the blood-brain barrier using MRI

Abstract

A method for measuring water exchange across the blood-brain barrier includes acquiring diffusion weighted (DW) arterial spin labeling (ASL) magnetic resonance imaging (MRI) signals. The method further includes determining optimal parameters to separate labeled water in capillary and brain tissue compartments. The method further includes estimating water exchange rate across the blood-brain barrier based on the DW ASL MRI signals and the optimal parameters, using a total generalized variation (TGV) regularized single-pass approximation (SPA) modeling algorithm.

What is claimed is: 
     
       1. A method for measuring water exchange across a blood-brain barrier based on diffusion weighted (DW) arterial spin labeling (ASL) magnetic resonance imaging (MRI) signals comprising:
 acquiring a plurality of diffusion weighted (DW) arterial spin labeling (ASL) magnetic resonance imaging (MRI) signals; 
 determining optimal parameters to separate labeled water in capillary and brain tissue compartments; and 
 estimating a water exchange rate across the blood-brain barrier based on the plurality of DW ASL MRI signals and the optimal parameters, using a total generalized variation (TGV) regularized single-pass approximation (SPA) modeling algorithm wherein the TGV is an enhanced framework for estimating a given arterial transit time (ATT) and the water exchange rate based on minimizing both first-order and second-order total variation (TV) for denoising the plurality of DW ASL MRI signals. 
 
     
     
       2. The method of  claim 1  wherein:
 the acquiring the plurality of DW ASL MRI signals further comprises acquisition of a set of DW ASL MRI signals using a diffusion prepared three-dimensional (3D) gradient and spin echo (GRASE) and a background suppressed pseudo continuous arterial spin labeling (pCASL), and 
 a diffusion preparation was implemented before the diffusion prepared 3D GRASE. 
 
     
     
       3. The method of  claim 1  wherein acquiring the DW ASL MRI signals includes formulating diffusion gradients in bipolar pairs along at least one of slice direction or other directions and optimizing timing to minimize eddy current. 
     
     
       4. The method of  claim 3  wherein acquiring the DW ASL MRI signals further includes applying an additional de-phasing gradient along a phase-encoding (PE) direction after the formulating diffusion gradients in bipolar pairs to induce a linear phase increment along the PE direction to dephase a non-Carr-Purcell-Meiboom-Gill (CPMG) signal that is affected by phase errors caused by bulk motion during a diffusion encoding. 
     
     
       5. The method of  claim 4  further comprising adding a pair of re-phasing and rewound dephasing gradients before and after each refocusing pulse to maintain CPMG condition and to balance a gradient moment. 
     
     
       6. The method of  claim 4  further comprising 3D turbo spin echo readout in conjunction with a de-phasing gradient after bi-polar gradients during diffusion preparation. 
     
     
       7. The method of  claim 1  wherein determining the optimal parameters includes selecting at least one of optimal b values or optimal diffusion weighting values. 
     
     
       8. The method of  claim 7  wherein selecting the at least one of the optimal b values or the optimal diffusion weighting values includes determining appropriate parameters which suppress capillary signals with minimal effects on tissue signals. 
     
     
       9. The method of  claim 1  further comprising estimating arterial transit time based on the DW ASL MRI signals and the optimal parameters. 
     
     
       10. A method for measuring water exchange across a blood-brain barrier comprising:
 acquiring a plurality of diffusion weighted (DW) arterial spin labeling (ASL) magnetic resonance imaging (MRI) signals using a diffusion prepared three-dimensional (3D) gradient and spin echo (GRASE) and background suppressed pseudo-continuous arterial spin labeling (pCASL); 
 determining optimal parameters to separate labeled water in capillary and brain tissue compartments including selecting at least one of optimal b values or optimal diffusion weighting values; and 
 estimating a water exchange rate across the blood-brain barrier based on the plurality of DW ASL MRI signals and the optimal parameters, using a total generalized variation (TGV) regularized single-pass approximation (SPA) modeling algorithm wherein the TGV is an enhanced framework for estimating a given arterial transit time (ATT) and the water exchange rate (k w ) based on minimizing both first-order and second-order total variation (TV) for denoising the plurality of DW ASL MRI signals. 
 
     
     
       11. The method of  claim 10  wherein a diffusion preparation was implemented before the 3D GRASE. 
     
     
       12. The method of  claim 10  wherein acquiring the DW ASL MRI signals includes formulating diffusion gradients in bipolar pairs along at least one of slice direction or other directions and optimizing timing to minimize eddy current. 
     
     
       13. The method of  claim 12  wherein acquiring the DW ASL MRI signals further includes applying an additional de-phasing gradient along a phase-encoding (PE) direction after the formulating diffusion gradients in bipolar pairs to induce a linear phase increment along the PE direction to dephase a non-Carr-Purcell-Meiboom-Gill (CPMG) signal that is affected by phase errors caused by bulk motion during a diffusion encoding. 
     
     
       14. The method of  claim 12  further comprising adding a pair of re-phasing and rewound dephasing gradients before and after each refocusing pulse to maintain CPMG condition and to balance a gradient moment. 
     
     
       15. The method of  claim 12  further comprising alternating a phase of refocusing pulses of 3D gradient and spin echo readout to minimize non-CPMG artifacts without applying a de-phasing gradient after bi-polar gradients during diffusion preparation. 
     
     
       16. The method of  claim 10  wherein selecting the at least one of the optimal b values or the optimal diffusion weighting values includes determining appropriate parameters which suppress capillary signals with minimal effects on tissue signals. 
     
     
       17. A method for measuring water exchange across a blood-brain barrier comprising:
 acquiring a plurality of diffusion weighted (DW) arterial spin labeling (ASL) magnetic resonance imaging (MRI) signals using a diffusion prepared three-dimensional (3D) gradient and spin echo (GRASE) and background suppressed pseudo-continuous arterial spin labeling (pCASL), and by formulating diffusion gradients in bipolar pairs along at least one of slice direction or other directions and optimizing timing to minimize eddy current; 
 determining optimal parameters to separate labeled water in capillary and brain tissue compartments including selecting at least one of optimal b values or optimal diffusion weighting values; and 
 estimating a water exchange rate across the blood-brain barrier based on the DW ASL MRI signals and the optimal parameters, using a total generalized variation (TGV) regularized single-pass approximation (SPA) modeling algorithm wherein the TGV is an enhanced framework for estimating a given arterial transit time (ATT) and the water exchange rate (k w ) based on minimizing both first-order and second-order total variation (TV) for denoising the plurality of DW ASL MRI signals. 
 
     
     
       18. The method of  claim 10  wherein the water exchange rate (k w ) comprises a capillary permeability surface-area product of water (PS w ) divided by a distribution volume of water tracer in a capillary space (V c ) that is calculated based on a monotonic relationship with a fraction of a capillary signal at the given arterial transit time (ATT).